Systematic review of molecular mechanism of action of negative-pressure wound therapy.

BACKGROUND: Negative-pressure wound therapy (NPWT) promotes angiogenesis and granulation, in part by strain-induced production of growth factors and cytokines. As their expression profiles are being unravelled, it is pertinent to consider the mode of action of NPWT at the molecular level. METHODS: MEDLINE (January 1997 to present), Embase (January 1997 to present), PubMed (no time limit), the Cochrane Database of Systematic Reviews and the Cochrane Controlled Trials Register were searched for articles that evaluated the influence of NPWT on growth factor expression quantitatively. RESULTS: Sixteen studies met the inclusion criteria. Tumour necrosis factor expression was reduced in acute and chronic wounds, whereas expression of interleukin (IL) 1ß was reduced in acute wounds only. Systemic IL-10 and local IL-8 expression were increased by NPWT. Expression of vascular endothelial growth factor, fibroblast growth factor 2, transforming growth factor ß and platelet-derived growth factor was increased, consistent with mechanoreceptor and chemoreceptor transduction in response to stress and hypoxia. Matrix metalloproteinase-1, -2, -9 and -13 expression was reduced but there was no effect on their enzymatic inhibitor, tissue inhibitor of metalloproteinase 1. CONCLUSION: Cytokine and growth factor expression profiles under NPWT suggest that promotion of wound healing occurs by modulation of cytokines to an anti-inflammatory profile, and mechanoreceptor and chemoreceptor-mediated cell signalling, culminating in angiogenesis, extracellular matrix remodelling and deposition of granulation tissue. This provides a molecular basis for understanding NPWT.

Management of severe open tibial fractures: the need for combined orthopaedic and plastic surgical treatment in specialist centres.

Although it is widely accepted that grade IIIB open tibial fractures require combined specialised orthopaedic and plastic surgery, the majority of patients in the UK initially present to local hospitals without access to specialised trauma facilities. The aim of this study was to compare the outcome of patients presenting directly to a specialist centre (primary group) with that of patients initially managed at local centres (tertiary group). We reviewed 73 consecutive grade IIIB open tibial shaft fractures with a mean follow-up of 14 months (8 to 48). There were 26 fractures in the primary and 47 in the tertiary group. The initial skeletal fixation required revision in 22 (47%) of the tertiary patients. Although there was no statistically-significant relationship between flap timing and flap failure, all the failures (6 of 63; 9.5%) occurred in the tertiary group. The overall mean time to union of 28 weeks was not influenced by the type of skeletal fixation. Deep infection occurred in 8.5% of patients, but there were no persistently infected fractures. The infection rate was not increased in those patients debrided more than six hours after injury. The limb salvage rate was 93%. The mean limb functional score was 74% of that of the normal limb. At review, 67% of patients had returned to employment, with a further 10% considering a return after rehabilitation. The times to union, infection rates and Enneking limb reconstruction scores were not statistically different between the primary and tertiary groups. The increased complications and revision surgery encountered in the tertiary group suggest that severe open tibial fractures should be referred directly to specialist centres for simultaneous combined management by orthopaedic and plastic surgeons.

Allogeneic skin substitutes applied to burns patients.

Early re-surfacing of burn wounds remains the ideal but is limited by the availability of skin graft donor sites. Cultured grafts overcome these problems and autologous keratinocytes can be grown in culture and placed on a dermal substitute, but this results in delay and requires two operations. We developed an organotypic skin substitute, which achieves cover in one procedure, and have previously found allogeneic cell survival up to 2.5 years after grafting onto clean elective wounds (tattoo removal). Here, we report a short series using the same model applied to burns patients with less than 20% total body surface area affected. The skin substitutes consisted of allogeneic dermal fibroblasts embedded in a collagen gel overlain with allogeneic epidermal keratinocytes, and were grafted to patients with tangentially excised burns. A side-by-side comparison with meshed split-thickness autografts was performed. No grafts became infected. The allogeneic skin substitute showed little effective take at 1 week, and by 2 weeks only small islands of keratinocytes survived. These sites were subsequently covered with meshed split-thickness autograft, which took well. It is concluded that further development of this model is needed to overcome the hostile wound bed seen in burns patients.

Cryopreservation of cultured dermal fibroblast impregnated collagen gels.

The survival of cultured dermal fibroblasts was evaluated following manufacture, freezing and disaggregation of fibroblast-impregnated collagen gels. The concentration which gave optimal cell survival was determined for three cryoprotectants (glycerol, dimethyl, sulphoxide (DMSO) and ethanediol) and their efficacy compared. DMSO led to the highest cell viability after freezing and thawing. The effect of rate of freezing was also compared and 0.5 degree C/min (within the range 20 degrees C to -70 degrees C) was found to result in a significant enhancement of cell viability in comparison with freezing at 1.0 degree C/min or rapid freezing.

Survival of allogeneic cells in cultured organotypic skin grafts.

Organotypic cultures of human skin were made using dermal fibroblasts seeded into a type I collagen gel overlaid with epidermal keratinocytes. Full-thickness excision of tattoos was performed on five patients, three of whom received sex-mismatched allografts. Patients were not immunosuppressed. Biopsies were obtained up to 3.5 years later. In situ hybridization of the PHY2.1 repetitive Y chromosome sequence revealed male fibroblasts and keratinocytes at 11 weeks and 2.5 years in the two female patients grafted with male cells. Structural components in the dermal substitute matured with time, and elastic fibers formed an interlacing meshwork by 18 months. Electron microscopy of the dermal-epidermal junction of an organotypic allograft revealed anchoring fibrils that had normal features at this time. Hyperemia of early grafts settled and contour correction was maintained, while repigmentation was variable. Hypertrophic scars did not occur, and graft contracture was never more than 20 percent. We conclude that this organotypic skin graft shows potential toward the goal of allogeneic skin replacement in a one-step procedure.

Closed continuous irrigation in the treatment of hand infections.

We report our experience with a closed continuous irrigation system in 12 patients with hand infections: six cases of flexor tenosynovitis, three cases of septic arthritis and three palmar abscesses. Four of these patients had undergone previous surgical debridement and peroperative washout without elimination of the infection. The continuous irrigation system consists of two fenestrated tubes placed within the infected space, with the tip of the smaller calibre inlet tube positioned just inside the larger outlet tube. Resolution of infection was achieved in all 12 cases and all regained complete functional recovery. The closed continuous irrigation system is easy to manage, with no leakage of fluid; hand therapy may be started early and the patient is mobile throughout.

Functional outcome following extensor synovectomy and excision of the distal ulna in patients with rheumatoid arthritis.

We prospectively measured hand and wrist function in rheumatoid patients undergoing excision of the distal ulna. Range of motion, visual analogue pain scores and grip strength were measured in 22 wrists, and the Jebsen hand function test was administered to seven patients, preoperatively and at 3 and 12 months. At 1 year there were improvements in forearm pronation (P=0.04), supination (P=0.03) and wrist extension (P=0.02), but a reduction in flexion (P=0.009). Active radial deviation was reduced and ulnar deviation increased. There was a significant improvement in grip strength (P=0.05) and reduction in wrist pain (P=<0.0001). At 1 year the Jebsen hand function test showed improvements in simulated feeding, stacking checkers, and lifting large empty cans. Excision of the distal ulna in rheumatoid patients results in an improvement in some aspects of hand function.

Synovial chondromatosis of the metacarpophalangeal joint.

We describe a case of synovial chondromatosis in a metacarpophalangeal joint with invasion of local structures. The degree of local tissue involvement was not demonstrated on the preoperative MRI scans. This case highlights that synovial chondromatosis can be invasive and that even the best preoperative imaging may not demonstrate this.

Pre-operative distraction lengthening for radial longitudinal deficiency.

Patients treated for total radial aplasia have been reviewed. It was possible to re-align the carpus by radialization in five out of six limbs treated with pre-operative distraction, but in only one out of six treated without distraction. The average improvement in radial angulation in the non-distraction group was 19 degrees and in the distraction group 38 degrees. The average improvement in radial translation was 16 mm and 17 mm in the two groups respectively. Pre-operative distraction with the Kessler device permits re-alignment of the hand without skeletal resection or excessive tension on the radial neurovascular structures.

Excision of the distal ulna in rheumatoid arthritis. Is the price too high?

Patients with rheumatoid arthritis who underwent excision of the distal ulna were reviewed and the operated wrist was compared with the non-operated side in the 40 patients who had the procedure performed unilaterally. Radiological assessment showed that the radiocapitate measurement of carpal translocation was the most consistent and that excision of the distal ulna was not associated with statistically significant collapse, ulnar translocation or radial rotation of the carpus. 61% of wrists spontaneously developed a radial shelf or limited radiocarpal fusion following excision of the distal ulna, compared to 21% of non-operated wrists. However, there was no statistically significant difference in carpal collapse or ulnar translocation between these two groups.

The provision of innervated skin cover for the injured thumb using dorsal metacarpal artery island flaps.

Provision of stable sensate skin is of great importance in reconstruction of the injured thumb. Island flaps based on the dorsal metacarpal arteries were used to resurface ten injured thumbs, and the degree of retained sensibility was assessed using static and moving two-point discrimination and the pick-up test. Results show that these flaps are capable of providing stable full-thickness skin cover in a single procedure and functional sensibility is retained in most cases. The second dorsal metacarpal artery island flap, previously advocated for use in small thumb defects only, has been successfully used as a large wraparound flap in two cases. In one of these it was used with free bone graft to increase the length of the thumb and an excellent functional result was achieved.

An approach to the management of radial longitudinal deficiency.

This paper describes an approach to the management of radial longitudinal deficiency. Early treatment includes manipulation and splintage prior to realignment of the carpus on the forearm. Twelve patients are presented in which a comparison is made between centralisation and radialisation surgical techniques. Preoperative distraction allowed radialisation without excision of a part of the carpus in five out of six patients. In contrast, centralisation with carpal excision was necessary in 5 out of 6 patients not treated by preoperative distraction. It remains to be seen whether radialisation is a superior procedure to centralisation in the longer term. However, radialisation in theory allows greater protection for the distal ulnar physis, maintains maximal length, and allows optimal wrist motion. Late treatment of radial longitudinal deficiency includes techniques of bone lengthening and correction of radial deviation deformity. Three cases are presented in which the Ilizarov technique was used to lengthen the forearm and to correct deformity. The complications of forearm lengthening are high but these techniques do allow significant correction of deformity.

The microbiological basis for a revised antibiotic regimen in high-energy tibial fractures: preventing deep infections by nosocomial organisms.

BACKGROUND: Deep surgical site infections (SSI's) complicate Gustilo IIIB tibial fractures in 8-13% of cases. Antibiotic prophylaxis typically covers environmental contaminants. However, nosocomial organisms are usually implicated in deep infection. We used the microbiological profile of infected Gustilo IIIB tibial fractures to define a new, dynamic prophylactic regimen which recognises the need for prophylaxis against nosocomial organisms at the time of definitive closure. METHODS: The microbiological profiles of Gustilo IIIB tibial fractures presenting over a 2-year period from January 2006 to December 2007 were reviewed. The environmental contaminants were compared with the organisms isolated from deep SSI's and correlated with the prophylactic antibiotic regimen used. RESULTS: Fifty-two patients were included. Nine developed a deep tissue infection. The pathogens implicated included resistant Enterococci, Pseudomonas, Enterobacter and MRSA. Standard antibiotic prophylaxis provided cover for these combinations in only one of nine cases. This would have improved to eight of nine cases with the use of teicoplanin and gentamicin, given as a one-time dose during definitive soft-tissue closure. Specimens taken from wound debridement were neither sensitive nor specific for the subsequent development of deep infection and did not predict the organisms responsible. CONCLUSIONS: Following high-energy open fracture, a single prophylactic antibiotic regimen directed against environmental wound contaminants does not provide cover for the organisms responsible for deepest SSI's and may have depopulated the niche, promoting nosocomial contamination prior to definitive closure. We advocate a dynamic prophylactic strategy, tailoring a second wave of prophylaxis against nosocomial organisms at the time of definitive wound closure, and at the same time avoiding the potential complications of prolonged antibiotic use.

Validation of a one-stop carpal tunnel clinic including nerve conduction studies and hand therapy.

INTRODUCTION: Carpal tunnel syndrome is the most common hand disorder. We describe a pathway that includes clinical assessment, neurophysiological testing, surgery and physical therapy all at the same visit. METHODS: All referrals for carpal tunnel syndrome were screened for inclusion in a 'one-stop' surgeon-led clinic. Prospective clinical data collected included patient reported outcome measures and satisfaction scores, touch threshold, pinch and grip strength. Patients were assessed clinically, underwent nerve conduction studies and surgery as indicated, all on the same day. Baseline and one-year follow-up data were analysed for 57 patients (62 hands). RESULTS: There was significant improvement in all domains of the Boston Carpal Tunnel and Michigan hand Outcomes questionnaires, grip strength and touch threshold. There were no adverse events. The total mean operating time was 12.8 minutes (range: 5-15 minutes) and the mean tourniquet time was 2.5 minutes (range: 1-11 minutes). Using a dual theatre model produced a short mean turnaround time of 14.8 minutes (range: 2-37 minutes). Patient satisfaction as judged using a Picker questionnaire was very high. CONCLUSIONS: A highly efficient clinical service involving both diagnostics and treatment can be delivered at a single hospital visit while maintaining optimal outcomes and high patient satisfaction.

Strategies to ensure success of microvascular free tissue transfer.

Free tissue transfer has revolutionised tissue reconstruction. Surgical technique is just one of many perioperative factors that determine the eventual outcome of the procedure. Many of these factors can be modified to ensure success. A search of the MEDLINE database using search terms related to perioperative management of free tissue transfer was performed. Further articles were identified by performing related-article searches in MEDLINE. The various perioperative factors that have been demonstrated to affect clinical outcome are discussed along with the current evidence for their optimisation. We present an algorithm for the management of patients undergoing free tissue transfer.